Postgraduate Medicine

ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20

Paraprotein-induced hyperviscosity
Michael D. Pavy, Patrick L. Murphy & Gabriel Virella
To cite this article: Michael D. Pavy, Patrick L. Murphy & Gabriel Virella (1980)
Paraprotein-induced hyperviscosity, Postgraduate Medicine, 68:3, 109-112, DOI:
10.1080/00325481.1980.11715533
To link to this article: http://dx.doi.org/10.1080/00325481.1980.11715533

Published online: 07 Jul 2016.

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Download by: [Australian Catholic University]

Date: 11 August 2017, At: 19:32

Paraprotein-inducecl
hyperviscosity
A reversible cause of stroke

Downloaded by [Australian Catholic University] at 19:32 11 August 2017

Michael D. Pavy, MD, Patrick L Murpby, MD, Gabriel Virella, MD, PhD

POSTGRADUATE MEDICINE im·ites submission of brief case reports, especiaUy
those related to ambulatory medical care. Illustrations and references should
be included only when essential.

A 60-year-old man was admitted for
evaluation of right hemiparesis. For
severa! weeks he bad experienced
general malaise and weakness; these
symptoms bad progressed to the
point where he bad become bedridden just before admission.
On admission the patient was stuporous. Blood pressure was 120/65
mm Hg, temperature 39 C (102 F),
and pulse rate 120 beats/min.
Physical examination was unremarkable except for right hemiparesis and right central paisy of the seventh cranial nerve. Results of la boratory studies showed a hemoglobin

leve! of 7.4 gmjdl; WBC count of
20,000/cu mm, with 54% polymorphonuclear leukocytes, 25% lymphocytes, 14% plasmablasts (figure
1), and 6% bands; and serum calcium leve! of 11.6 mg/dl.
Cellulose acetate serum electrophoresis disclosed a gamma globulin
leve! of 8.75 gmjdl. Immunoelectrophoretic studies showed the monoclonal spike present in the serum to
be IgG 2-K. This paraprotein bad the
characteristics of a pyroglobulin (ie,
polymerization at 56 C [ 132.8 F]).
Levels of other major immunoglobulins were depressed, with an lgA
continued

Figure 1. Peripheral smear showing plasmablast and rouleau formations typical of the
hyperviscosity syndrome. (Wright-Giemsa x 1,000)

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109

Downloaded by [Australian Catholic University] at 19:32 11 August 2017

CASE REPORT CONTINUED

leve! of 15 mg/ dl and an IgM leve! of
50 mg/dl. Serum viscosity was 4.3
relative to water (normall.2 to 1.4),
determined using the Hess-Martinet capillary viscometer.
A chest x-ray film showed pneumania in the left upper lobe. Sputum
cultures grew Klebsiella pneumlr
niae and Proteus mirabilis. Computed tomographie scanning of the
head showed mild atrophy of the cerebral cortex without focal abnormalities.
Treatment with methylprednisolone and gentamicin was started. On
the second hospital day the patient
was still stuporous. Six units of
whole blood were drawn and replaced with packed red cells and
normal plasma. The patient became
somewhat more alert, the right
hemiparesis partially resolved, and
serum viscosity decreased to 2.4.
Over the next two days, mental
status progressively deteriorated,
and serum viscosity rose to 2.9. The
patient underwent direct plasmapheresis via a centrifugai blood separation deviee (Aminco Cell Separator) for four hours. This resulted in
complete resolution of hemiparesis,
return of mental status to normal, a
fall in serum viscosity to l. 7, and a
decrease in gamma globulin to 3.75
gm/dl.
Over the next severa! days the patient showed progressive deterioration in mental status, recurrence of
right hemiparesis, and a rise in serum viscosity to 3.0. Proteus pneu-

110

monia developed in the right lower
lobe and he died.
Autopsy disclosed plasma cell leukemia involving the bone marrow,
lungs, spleen, pancreas, and kidneys.
Examination of the brain showed
encephalomalacia with multiple
smalllacunar infarcts.

DiscaBSion
Whole blood viscosity is dependent
upon the concentration of and interaction between serum proteins and
the formed elements of the blood.
This interaction is most significant
at the microvascular leve!, where
flow rates of blood are low and intermittent. This fact makes in vitro viscosity measurements difficult to correlate with clinical symptoms. 1 The
leve! of serum viscosity at which
symptoms are seen varies with the
individual, but within each patient
there is a "symptomatic threshold"
above which a major end-organ system will consistently demonstrate
clinical abnormalities. 2 The case reported here followed this general
Michael D. Pary
Patrick L Murphy
Gabriel Virella
Dr Pavy was formerly clinical instructor,
Medical University of South Carolina College of Medicine, Charleston, and is now clinica! assistant, depart ment of oncology, the
Johns Hopkins Oncology Center, Baltimore.
Dr Murphy is a medical resident, department
of medicine, and Dr Virella an associate
professer, department of basic and clinical
immunology and microbiology, Medical University of South Carolina College of Medicine.

rule, and the patient manifested
neurologie deterioration at a serum
viscosity of 2.9.
The neurologie manifestations of
the hyperviscosity syndrome vary
from headache to coma3 but are generally not focal in character. Headache, dizziness, and true vertigo typically occur, and occasionally generalized seizures are present. 4 The
hemiparesis in the case described
was likely due to paraprotein-induced blood-flow sludging, since it
correlated clinically with changes in
serum viscosity. In a previous report,3 patients with neurologie presentations of hyperviscosity frequently had other characteristics of
this syndrome, such as bleeding diathesis, funduscopic changes, and
expanded plasma volume. 4 The case
of our patient is unique in that other
clinical findings of hyperviscosity
were lacking and thus plasmapheresis was delayed.
The common concept that hyperviscosity is seen predominantly in association with IgM gammopathies
needs to be revised, since the occurrence of hyperviscosity in association with IgG 5 or IgN gammopathies is far from infrequent. In the
period from 1975 to 1979, we at the
Medical University of South Carolina saw 13 patients showing dysproteinemia with serum viscosities in
excess of 3.0 (relative to distilled
water). Of these 13, seven had IgG
monoclonal gammopathy, three IgA
gammopathy, two polyclonal hypercontinued

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Downloaded by [Australian Catholic University] at 19:32 11 August 2017

CASE RliPORT CONTINUED

gammaglobulinemia, and one lgM
monoclonal gammopathy. The highest viscosity recorded (5.0) was in a
patient with lgA gammopathy.
Moreover, in six patients with symptomatic hyperviscosity who we studied in detail, gammopathies were
equally distributed among the three
major immunoglobulin classes (two
classified as lgG, two as lgA, and
two as lgM).
Another misconception raised in
earl y reports was that of the predominance of IgG 1 and lgG 3 paraproteins in those cases of hyperviscosity
associated with lgG multiple myeloma.6·7 Actually, in a series
of 22 cases of hyperviscosity associated with lgG gammopathy studied
by one of us (G. V.), 8 the distribution
among subclasses was similar to that
usually found on a random basis; in
the present case the paraprotein was
of the lgG 2 subclass, and the hyperviscosity was probably due to a combination of factors, such as extremely high serum concentration
and abnormal configuration (as suggested by the tendency toward polymerization at 56 C).
Conclusion
Altbough the occurrence of the hypeniscosity syndrome with IgG
plasma ceU leukemia is unusual, it
should be considered in the evaluation of patients with focal neurologie
deficit with or witbout a known malignant paraproteinemia. If serum

112

viscosity is elevated, theo emergent
plasmapheresis should be considered,
as it may reverse the neurologie
deficit.. . .
Addrcss reprint rcquests to Michael D. Pavy,
MD, Dcpartment of Oncology, The Johns
Hopkins Oncology Center, 601 N Broadway,
Baltimore, MD 21205.

References
1. McGratb MA. Penny R. Paraproteinemia:
blood hypcrviscosity and clinical manifesta·
tians. J Clin lnvest 1976;58: 1155-62
l. Fabey JI.., Butb WF, Solomoa A. Serum
hypcrviscosity syndrome. JAMA 1965;
192:464-7
3. Azzena D, Costa U, Cbingliotti G, et aL Se-

rum hypcrviscosity in multiple myeloma and
its clinical and neuropsychiatrie implications.
Con lin Neural 1968;30:65-76
4. Blocb KJ, Maki DG. Hypcrviscosity syndromes associatcd with immunoglobulin abnormalities. Sernin Hematoll973;10:113-24
S. Pruzansk.i W, Wan JG. Serum viscosity
and hypcrviscosity syndrome in IgG multiple
myeloma: report on 10 patients and a review
of the literature. Ann Intem Mcd 1972;
77:853-60
6. Virella G, Fudenberg HH. Polymerizcd
lgA and serum hypcrviscosity syndrome in
human and animal multiple myeloma. La
Riccrca Clin Lab 1976;6(Suppl 3): 125
7. Capra JD, KIDikel HG. Aggregation of
gamma-G3 proteins: relevancc to the hypcrviscosity syndrome. J Clin Invest 1970;
49:610-21
8. Virella G. Hcavy chain subclasscs of human immunoglobulin G. (Doctoral thesis.)
Lisbon: Gulbcnkian Foundation, 1973

Dr Tom Swlr- ...

"Tao bad you don't have any flowers in your hospital room," said Dr Tom,
lackadaisically.
Alan E. Lindsay, MD
Salt Lake City
"You will have to stop eating processed cheese," said Dr Tom kraftily.
/.Jack Markens, MD. Toronto
"This bite could lead to rabies," said Dr Tom, doggedly.
Donald K. Haynes, MD
Homer, LA
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Address: Editorial Department, POSTGRADUATE MEDICINE,
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ITROKI! DUE TO ltYPBIYI8C08rTY • VOL 68/NO 3/SEPTEMBER 1980/POSTGRADUATE MEDICINE